Genes associated with dimorphism and virulence ofCandida albicans

Abstract

Strategies for the analysis of a range of Candida albicans genes, whose expression is regulated during the yeast to hyphal transition (dimorphism), including genes encoding putative virulence factors, are reviewed. To help discriminate among genes whose products were the cause or consequence of dimorphism, temporal changes in the levels of the mRNAs of these and other genes were examined by northern analysis. The mRNA levels of most genes that were examined increased or decreased, transiently or persistently indicating complex alterations in gene expression during morphogenesis. Genes encoding four glycolytic enzymes were regulated transcriptionally during dimorphism but control experiments indicated no direct correlation with germ tube formation. Two chitin synthase genes (CHS2 and CHS3) and three aspartyl proteinase genes (SAP4–SAP6) were transcribed preferentially in the hyphal form, but in these cases hypha-specific expression was shown to be strain dependent or medium dependent, respectively. A gene, HYR1 (for hyphal regulation), was isolated and found to exhibit strict hypha-specific expression in a range of strains under a range of culture conditions. The ura-blaster protocol was used to generate disruptions in CHS2, CHS1, and HSP90 (for heat-shock protein). The homozygous CHS2 disruption did not affect the kinetics of germ-tube formation markedly but resulted in hyphae with a reduced chitin content. In contrast, homozygous null mutations in CHS1 and HSP90 were apparently lethal because no homozygous null strains were isolated after integrative transformation of heterozygous mutants. The analysis of candidate genes for dimorphism and virulence of C. albicans through northern analysis and gene disruption should facilitate an understanding of these processes at the molecular level. Key words: Candida, dimorphism, gene regulation, virulence.